The hydrogen bond is a key structural feature of biomolecules. The objective of the proposed research is to determine experimentally the symmetry of a variety of hydrogen bonds. A fundamental question is whether the hydrogen is located midway between the two donor atoms or is closer to one of them and jumping back and forth between them. Both situations have been observed. Previous methods include microwave spectroscopy, applicable to the gas phase, and X-ray and neutron diffraction, applicable to crystals. The novel NMR Method of Isotopic Perturbation of Equilibrium now permits the study of hydrogen bond symmetry in solution, even the aqueous ones that are crucial for biological systems. Various molecules have been designed to explore the diversity of hydrogen bond situations. One key feature is the distance between the donor atoms. Another is the polarity or disorder of the solvent. These will be varied, along with the nature of the donor atoms, the electronic asymmetry due to substituents, and the charge type. The proposed experiments will provide a systematic study of the symmetry of hydrogen bonds, especially those that are found in proteins. The results will be of broad significance for our understanding of biomolecular structure and of enzymatic action and for design of molecules to exhibit intermolecular recognition. Such information is essential for understanding interatomic distances and interatomic forces in biomolecules, and for designing organic compounds with potential biochemical, chemotherapeutic, and pharmacological activity.